This is an application for support for a SCOR in Osteoarthritis at Rush-Presbyterian-St. Luke's Medical Center in Chicago. It represents a closely related and integrated program entitled "Osteoarthritis: A Continuum (From Cartilage Metabolism to Early Detection and Treatment"). The major theme, focusing on the investigative specificity of certain aspects of the disease process, will be explained at several levels of biological organization: The structural or molecular level with respect to cartilage matrix molecules, the cellular level both in relation to anabolism and catabolism, and the tissue level in expressing the integrated response of biomechanical criteria to the joint as an organ. Within this context, the proposal addresses the questions of structural and functional biochemistry of cartilage matrix and chondrocyte metabolism as it relates to subpopulations of cells and thus to the onset and detection of the disease; it focuses on the response of normal cartilage and chondrocytes to a variety of biochemical and biomechanical stimuli; and it studies the endogenous defense mechanism of the tissue against exogenous enzymatic attack. As we have accumulated knowledge on cartilage metabolism at the molecular level, studies directed toward fulfilling the need to establish biochemical markers of disease activity (e.g., keratan sulfate in patient's serum) will be established and analyses of the functional biomechanics of patients before and after surgical treatment of osteoarthritis undertaken. To address these issues funding for five projects and three supportive core facilities is requested. Investigators are drawn from five academic departments: Department of Biochemistry, (including laboratory of molecular biology); Department of Orthopedic Surgery, (including the programs in biomechanics and biochemistry); Department of Medicine (Section of Rheumatology); Department of Pathology; and Department of Anatomy. At the present time substantial interactions and collaborations are already taking place, making Rush a optimal site for the SCOR in Osteoarthritis.